By using an in vitro system in which spleen cells of unprimed rabbits of known allotypes are stimulated with a soluble T2 phage antigen preparation, we have obtained evidence supporting the idea that chronic allotype suppression in the rabbit is the result of a specific active suppression mechanism. We now propose a continuation of these studies in order to seek more precise infomation regarding the origin and mechanism of the suppressive action, as well as the events which occur during release from suppression, both spontaneous and induced. To pursue these objectives we have outlined experiments to test the hypothesis that suppression is maintained by means of a suppressor cell or factor with specific reactivity against cells or molecules bearing the suppressed determinant. Alternate hypotheses will also be examined. The nature of suppression will be investigated by testing for direct demonstrations of the transfer of active suppression both in vitro and in vivo, using rabbits matched for major histocompatibility antigens. Cell separation procedures based on immunologically specific as well as non-specific principles will be incorporated into these experiments in attempts to identify the suppressive cell or factor. We shall also probe the nature of suppression by analyzing Ig expression of cells undergoing release for suppression in vivo, both spontaneous and induced by various means. Information obtained in the proposed study could advance our general understanding of the means by which Ig-forming cells are regulated and thus have relevance to such human conditions as immunodeficiency diseases, auto-immune states, and allergies.